Obesity is a public health problem globally, and two-thirds of US men are overweight or obese. For prostate cancer patients, the obesity epidemic is of concern since men who are overweight before or at the time of diagnosis are at increased risk of biochemical recurrence and cancer-specific mortality. There are several outstanding questions underlying the association between obesity and lethal prostate cancer whose answers are needed to shed light on the translational potential among prostate cancer patients. Our study aims to elucidate mechanisms underlying the link between obesity and lethal prostate cancer and identify patient subgroups more susceptible to the obesity milieu. We hypothesize that obesity may act through local tumor effects which are